Bitter taste receptors in the lungs could revolutionize asthma treatment

Bitter taste receptors in the lungs could revolutionize asthma treatment

Bitter taste receptors we have in our mouths were found to also exist in our lungs - what researchers discovered about these functioning receptors in the smooth muscle of the bronchus in the lungs may transform future treatment for asthma and obstructive lung diseases, scientists wrote in an article published in Nature Medicine. When bitter taste receptors in the lungs were exposed to certain doses of substances known to activate bitter taste receptors in the tongue, they opened up the airways better than most current medications are able to do.

Senior author, Stephen B. Liggett, M.D., a pulmonologist from the University of Maryland School of Medicine, said:

The detection of functioning taste receptors on smooth muscle of the bronchus in the lungs was so unexpected that we were at first quite skeptical ourselves.

Dr. Ligget explains that he and his colleagues discovered the existence of functioning bitter taste receptors in the lungs accidently during a previous and unrelated study which was examining how lung muscle receptors regulate airway tightening and expansion.

Air travels in and out of the lungs through the airways, one of the key steps for cell oxygen delivery throughout the human body. The smooth muscle airways tighten up when a patient has an asthma episode, undermining airflow and resulting in shortness of breath and wheezing, the authors explain.

The bitter taste buds in our tongue exist in clusters and send signals to the brain. The ones in the lungs do not exist in clusters, neither do they communicate bitter tastes with the brain - however, they are otherwise identical to those in the tongue; when exposed to substances with a bitter taste they respond in the same way.

In this latest study, Ligget and team exposed the airways and smooth muscle cells in the airways of humans and mice to bitter-tasting compounds. They also exposed the airways of mice with asthma to bitter-tasting compounds.

The scientists believe that the taste receptors in the lungs have the same purpose as those in our tongue - to warn against toxins.

Ligget said:

I initially thought the bitter-taste receptors in the lungs would prompt a 'fight or flight' response to a noxious inhalant, causing chest tightness and coughing so you would leave the toxic environment, but that's not what we found.

Our bitter taste receptors can be activated by thousands of non-toxic compounds if the doses are right. Some are natural, such as those from berries, trees or flowers, while others are synthetic.

Some of these substances, known to activate bitter taste receptors were used. The scientists were surprised that when the taste receptors were activated, the airways opened up.

Ligget explained:

It turns out that the bitter compounds worked the opposite way from what we thought. They all opened the airway more extensively than any known drug that we have for treatment of asthma or chronic obstructive pulmonary disease (COPD).

Dr. Ligget and team are convinced that new therapies which work by activating the bitter taste receptors in the lungs, and consequently opening up the airways could transform future treatment for asthma, chronic bronchitis and emphysema. This could either replace current therapies, or improve them.

Chloroquine and quinine, very bitter substances, were found to open up the airways in mice with asthma - when their airways had been tightened up during an asthma attack. Saccharin, a sweetener with a bitter aftertaste, also relaxed the airways in mice with asthma.

Eating bitter foods will not have the desired effect, the scientists warn.

Ligget said:

Based on our research, we think that the best drugs would be chemical modifications of bitter compounds, which would be aerosolized and then inhaled into the lungs with an inhaler.

Another surprise was when they found that bitter compounds cause calcium levels to rise. They expected this to cause further contraction of the airways, but the opposite happened.

Principal author, Deepak A. Deshpande, Ph.D., an expert in how calcium controls muscles, said:

We always assumed that increased calcium in the smooth muscle cell caused it to contract, but we found that bitter compounds increase calcium and cause relaxation of airway muscle in a unique way. It appears that these taste receptors are wired to a special pool of calcium that is right at the edge of these cells.

E. Albert Reece, M.D., Ph.D., M.B.A., vice president for medical affairs at the University of Maryland and dean of the University of Maryland School of Medicine, said:

The work of this team exemplifies what it takes to make real improvements in treating certain diseases. These researchers were willing to take chances and ask questions about an unlikely concept. Why are taste receptors in the lungs? What do they do? Can we take advantage of them to devise a new therapy? In the end, their discoveries are in the best tradition of scientific research.

"Bitter taste receptors on airway smooth muscle bronchodilate by localized calcium signaling and reverse obstruction"

Deepak A Deshpande, Wayne C H Wang, Elizabeth L McIlmoyle, Kathryn S Robinett, Rachel M Schillinger, Steven S An, James S K Sham & Stephen B Liggett

Nature Medicine Year published: DOI: doi:10.1038/nm.2237

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Section Issues On Medicine: Disease